INTRODUCTION: Cathepsin B is of significant importance to cancer therapy as it is involved in various pathologies and oncogenic processes in humans. Numerous studies have shown that abnormal regulation of cathepsin B overexpression is correlated with invasive and metastatic phenotypes in cancers. Cathepsin B is normally associated with the lysosomes involved in autophagy and immune response, but its aberrant expression has been shown to lead to cancers.AREAS COVERED: This review highlights the oncogenic role of cathepsin B, discusses the regulation of cathepsin B in light of oncogenesis, discusses the role of cathepsin B as a signaling molecule, and highlights the therapeutic potential of targeting cathepsin B.EXPERT OPINION: Targeting cathepsin B alone does not appear to abolish tumor growth, and this is probably because cathepsin B appears to have diverse functions and influence numerous pathways. It is not clear whether global suppression of cathepsin B activity or expression would produce unintended effects or cause the activation or suppression of unwanted pathways. A localized approach for targeting the expression of cathepsin B would be more relevant. Moreover, a combination of targeting cathepsin B with other relevant oncogenic molecules has significant therapeutic potential.